Antenatal montelukast treatment reduces uterine activity associated with inflammation in a pregnant rat model. (November 2016)

• Record Type: Journal Article
• Authors: Corriveau, Stéphanie; Blouin, Simon; Burt, Elyse; Rousseau, Eric; Pasquier, Jean-Charles
• Is Part Of: European journal of obstetrics, gynecology, and reproductive biology. Volume 206(2016:Nov.)
• Page Start: 92
• Page End: 98
• Publication Date: 2016-11
• Subjects: Inflammation -- Leukotrienes -- Montelukast -- Pregnant rats -- Tocolytics -- Uterine contractions; Obstetrics -- Periodicals; Gynecology -- Periodicals; Reproductive health -- Periodicals; Gynecology -- Periodicals; Obstetrics -- Periodicals; Reproduction -- Periodicals; Obstétrique -- Périodiques; Gynécologie -- Périodiques; Reproduction -- Périodiques; Verloskunde; Gynaecologie; Voortplanting (biologie); Gynecology; Obstetrics; Reproduction; Electronic journals; Periodicals; Electronic journals; 618.05
• DOI: 10.1016/j.ejogrb.2016.08.003
• Languages: English
• ISSNs: 0301-2115

Abstract

Abstract: Objective: The potency of acute montelukast treatment, a leukotriene receptor antagonist, has been demonstrated as tocolytic on in vitro myometrial contractility. This study assessed the ability of a 48 h montelukast treatment to modify in vitro contractions under inflammatory conditions in a pregnant rat model. Study design: Pregnant Sprague-Dawley rats were injected intraperitoneally (gestational days 20–22) with lipopolysaccharides (LPS) 200 μg/kg (4 treatments at 12 h intervals) alone or combined with montelukast 10 mg/kg/day or a saline solution for a 48 h period. Uterine rings ( n = 72) were obtained by median laparotomy at day 22. Spontaneous contractile activities were compared using pharmacological compounds (oxytocin, nifedipine) along with assessment of contractile parameters. Myometrial subcellular fractions were also analyzed by Western blot to quantify oxytocin, cysteinyl leukotriene receptors and inflammation markers. Results: In in vitro experiments, the area under the curve, the amplitude and the duration of phasic contractions were significantly reduced following 48 h of LPS + montelukast treatment comparatively to the LPS group. Moreover, in this same group, oxytocin (10 −9 –10 −7 M) largely decreased uterine sensitivity ( p = 0.04). Following LPS and montelukast treatment, the tocolytic effectiveness of nifedipine (10 −9 –10 −7 M) was increased ( p < 0.01). Western blot analysis confirmed the presence of type 1 CysLT receptors in all treated groups. Hence, montelukast treatment restored TNF-α and COX-2 basal levels. Conclusion: Our results strongly suggest that montelukast treatment could facilitate a relative uterine quiescence by decreasing its sensitivity to uterotonic agent or by increasing tocolytic efficiency under proinflammatory conditions.